Pembrolizumab Receives FDA Approval to Treat TMB-H Tumors

Pembrolizumab Receives FDA Approval to Treat TMB-H Tumors

For treating adult and pediatric patients having metastatic or unresectable tumor mutational burden-high (TMB-H) [defined as ≥10 mutations/megabase (mut/Mb)] solid tumors, as authenticated by a Food and Drug Administration (FDA)-approved test, that have advanced following prior treatment and who have no adequate alternatives, pembrolizumab received FDA approval on 16 June 2020.

The FoundationOneCDx assay was also granted approval as a companion diagnostic tool for pembrolizumab. A prospectively-planned, multicentre, non-randomized, open-label retrospective trial (KEYNOTE-158) aimed to explore the efficacy of pembrolizumab in 10 cohorts of patients suffering from various previously cured unresectable or metastatic TMB-H solid tumors.

Participants were given an intravenous (IV) infusion of 200 mg pembrolizumab every 3 weeks until disease advancement or unacceptable toxicity. The primary endpoints were duration of response and overall response rate (ORR) in patients who have been given at least one pembrolizumab dose. The dose was assessed by blinded independent central review based on Response evaluation criteria in solid tumors (RECIST) v1.1. This was altered to follow a maximum of ten target lesions and a maximum of five target lesions per organ.

Overall, 102 (13%) subjects had tumors recognized as TMB-H solid tumors. The ORR, complete and partial response rate is depicted in the following table:


Complete response rate

Partial response rate

29 %

4 %

25 %

The median duration of response was not attained. The percentage of patients having response durations ≥12 and ≥24 months is shown in the following table:

Response duration ≥12 months

Response duration ≥24 months

% of patients

57 %

50 %

Patients suffering from TMB-H cancer recruited in the KEYNOTE-158 witnessed similar adverse reactions as in patients having other solid tumors who were given pembrolizumab as a single therapeutic. Pyrexia, musculoskeletal pain, diarrhea, pruritus, nausea, rash, fatigue, constipation, dyspnoea, abdominal pain, cough, and decline in appetite are common side effects of pembrolizumab.

Pembrolizumab is linked with immune-mediated adverse reactions such as pneumonitis, nephritis, hepatitis, endocrinopathies, colitis, and skin side effects. A “Limitation of Use” has been incorporated in the prescribing information. It illustrates that the safety and efficacy of pembrolizumab in pediatrics having TMB-H central nervous system tumors have not been yet ascertained.

For managing patients having TMB-H solid tumors, the pembrolizumab’s dose is suggested to be 2 mg per kg (up to a maximum of 200 mg) every three weeks for pediatrics, and 200 mg every three weeks or 400 mg every six weeks for adult patients.




Original title of the article

FDA approves pembrolizumab for adults and children with TMB-H solid tumors


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